title: Generation of MHC class I ligands in the secretory and vesicular pathways.
abstract: CD8(+) T lymphocytes screen the surface of all cells in the body to detect pathogen infection or oncogenic transformation. They recognize peptides derived from cellular proteins displayed at the plasma membrane by major histocompatibility complex (MHC) class I molecules. Peptides are mostly by-products of cytosolic proteolytic enzymes. Peptidic ligands of MHC class I molecules are also generated in the secretory and vesicular pathways. Features of protein substrates, of proteases and of available MHC class I molecules for loading peptides in these compartments shape a singular collection of ligands that also contain different, longer, and lower affinity peptides than ligands produced in the cytosol. Especially in individuals who lack the transporters associated with antigen processing, TAP, and in infected and tumor cells where TAP is blocked, which thus have no supply of peptides derived from the cytosol, MHC class I ligands generated in the secretory and vesicular pathways contribute to shaping the CD8(+) T lymphocyte response.
authors.affiliation: Unidad de Inmunología Viral, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Nicolás Cabrera 1, Universidad Autónoma de Madrid, Campus Cantoblanco, 28049 Madrid, Spain, mdval@cbm.uam.es
authors.forename: Margarita
authors.initials: M
authors.lastname: Del Val
authors.forename: Salvador
authors.initials: S
authors.lastname: Iborra
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos
authors.forename: Silvia
authors.initials: S
authors.lastname: Lázaro
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001692:Biological Transport / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008024:Ligands; D026901:Membrane Transport Proteins / Q000276:immunology; D051379:Mice; D010447:Peptide Hydrolases / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D055571:Secretory Pathway / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D026901:Membrane Transport Proteins; D010455:Peptides; D010447:Peptide Hydrolases